PROPANEDIOL MONOACETATE MONONITRATE

Abstract

The present invention relates to propanediol monoacetate mononitrate as well as the use thereof as antimicrobial agent, in particular for cosmetic applications.

Claims

1. Propanediol monoacetate mononitrate of formula (I) ##STR00002##

2. Use of propanediol monoacetate mononitrate as antimicrobial agent.

3. The use according to claim 2, wherein the antimicrobial agent is an antifungal and/or antibacterial agent.

4. The use according to claim 3, wherein the antifungal and/or antibacterial agent is an agent that inhibits the growth of S. epidermis, C. xerosis, M. furfur and P. acnes as well as mixtures thereof.

5. The use according to claim 2 in cosmetic or pharmaceutical applications.

6. The use according to claim 2 for improving preservation.

7. Non-therapeutic use of propanediol monoacetate mononitrate to maintain skin homeostasis and/or balance the skin microbiome.

8. Non-therapeutic use of propanediol monoacetate mononitrate as deodorant active compound.

9. Propanediol monoacetate mononitrate for use as anti-acne compound.

10. Propandiol monoacetate mononitrate for use in the treatment, prevention and/or prophylaxis of Pityriasis versicolor, dandruff formation, seborrheic dermatitis, atopic dermatitis and psoriasis

11. A cosmetic or pharmaceutical composition comprising propanediol monoacetate mononitrate.

12. The cosmetic or pharmaceutical composition according to claim 11, wherein the amount of propanediol monoacetate mononitrate is selected in the range of about 0.005 to 2 wt.-%, preferably 0.01 to 1 wt.-%, more preferably in the range of about 0.05 to 0.75 wt.-% and most preferably in the range of 0.1 to 0.5 wt.-%, based on the total weight of the composition.

13. A non-therapeutic method for killing and/or inhibiting growth of microbial cells, in particular fungal and/or bacterial cells, said method comprising contacting said microbial cells with propanediol monoacetate mononitrate.

14. Process for the preparation of propanediol monoacetate mononitrate, said process encompassing the step of reacting 1,3-propandiol monoacetate with nitrosulfuric acid.

15. The process according to claim 14, wherein the process is carried out in an inert organic solvent.

Description

EXAMPLE 1: PREPARATION OF PROPANEDIOL MONOACETATE MONONITRATE (PDMAMN)

[0061] 1,3-propandiol monoacetate (PDMA) in dichloromethane (800 g/h, 40%, 2.7 mol PDMA/h) and nitrosulfuric acid (830 g/h, consisting of 2 mol sulfuric acid (98%) per mol of fuming nitric acid, 3.24 mol HNO3/h) were continuously dosed to a microreactor at 0° C. applying a residence time of 11 seconds. Then the mixture is quenched with water (4.1 kg/h) at 15° C. and further neutralised using a sodium hydroxide solution (1.14 kg/h containing 28% NaOH in water). The partially neutralised reaction mixture is collected in a flask for 120 seconds (225 g). The aqueous phase was separated and the organic phase three times washed with water (3×45 ml) and the solvent evaporated in vacuo. Yield: 99% (14.8 g; 98% purity as determined by HPLC).

EXAMPLE 2 ANTIMICROBIAL EFFICACY

[0062] The antimicrobial efficacy of propanediol monoacetate mononitrate (PDMAMN) is assessed in analogy to the regulatory challenge test method (NF EN ISO11930). The following test solutions were tested [0063] 1. Inv 1: 400 mg PDMAMN in 1 ml PEG 400 were diluted with 40 mL physiological serum (0.85% NaCl) containing 7% Ethanol (˜1% of PDMAMN) [0064] 2. Inv 2: 200 mg PDMAMN in 1 ml PEG 400 were diluted in 40 mL physiological serum (0.85% NaCl) containing 7% Ethanol (˜0.5% of PDMAMN) [0065] 3. Inv 3: 40 mg 3-PDMAMN in 1 ml PEG 400 were diluted in 40 mL physiological serum (0.85% NaCl) containing 7% Ethanol (˜0.1% of PDMAMN) [0066] 4. Ref 1: Physiological serum (0.85% NaCl) [0067] 5. Ref 2: 1 mL PEG 400+40 mL physiological serum (0.85% NaCl) containing 7% Ethanol [0068] 6. Control: 0.5% Phenonip in physiological serum (0.85% NaCl)

[0069] All test solutions were deposed in 96-deep well plates (1.6 ml/well). The wells were contaminated with the respective bacterial or the fungal strains as outlined in table 1*10.sup.5 to 1*10.sup.6 cfu/ml for the bacteria and 1*10.sup.4 to 1*10.sup.5 cfu/ml for the fungi to obtain the initial contamination as outlined in table 1, Zero. After the contamination, each well was thoroughly mixed to ensure a homogeneous distribution of the microorganism. Then each plate was incubated at 22° C. for 24 h. The counting of the (remaining) population was carried out 24 h after contamination.

TABLE-US-00001 TABLE 1 Zero Inv 1 Inv 2 Inv 3 Ref 1 Ref 2 Control colony counts [cfu/ml] S. epidermidis 500000 0 0 0 500000 400000 0 (deo, gram+) C. xerosis 250000 0 0 0 250000 250000 0 (deo, gram+) M. furfur 4000 0 0 0 40000 40000 0 (dandruff, yeast) P. Acnes 100000 0 0 0 100000 100000 0 (acne, gram+)

[0070] As can be seen in the table above propanediol monoacetate mononitrate exhibits an excellent antimicrobial activity, almost comparable to Phenonip™, a broad spectrum antimicrobial agent designed for preservation of a wide range of cosmetics and toiletries.